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Diversity of structural, dynamic, and environmental effects explain a distinctive functional role of transmembrane domains in the insulin receptor subfamily

Human InsR, IGF1R, and IRR receptor tyrosine kinases of the insulin receptor subfamily play an important role in signaling pathways for a wide range of physiological processes. Sharing high sequence and structure homology, the receptors differ dramatically in their localization, expression, and functions. A team of scientists from IBСH RAS in cooperation with colleagues from other institutions using the high-peroscopy of high resolution and computer modeling established that the conformational variability of transmembrane domains and their interaction with surrounding lipids differ significantly among representatives of the subfamily.

Bershatsky YV, Kuznetsov AS, Idiatullina AR, Bocharova OV, Dolotova SM, Gavrilenkova AA, Serova OV, Deyev IE, Rakitina TV, Zangieva OT, Pavlov KV, Batishchev OV, Britikov VV, Usanov SA, Arseniev AS, Efremov RG, Bocharov EV

Thus, the heterogeneous membrane environment should be taken into account in the diverse activation mechanisms of InsR, IGF1R, and IRR. This membrane-mediated control of receptor signaling offers an attractive prospect for the development of new targeted therapies for diseases associated with dysfunction of insulin subfamily receptors.

The results are published in the International Journal of Molecular Sciences.


february 28